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Biomedical subjects

T W van den Akker

Publications and source records attributed to T W van den Akker.

At least 19 recordsLinked to original sources
PubMed2001

[Lichen planus, a T-lymphocyte mediated reaction involving the skin and mucous membranes].

Lichen planus concerns a benign skin disorder without involvement of other organ systems. Its course is generally limited to less than a year. Classic lichen planus is characterized by pruritic, violaceous, plane papules which occur most commonly on the inside of the wrists, the lower back, the lower legs and the perimalleolar region of adults aged between 30-60 years. Frequently, oral and genital mucous membrane lesions are involved. Erosive mucosal lesions are particularly painful and long-lasting. Many clinical variants have been described ranging from lichenoid drug eruptions to associations with graft-versus-host disease. The cause of lichen planus is unknown. An immunopathological pathogenesis with T-lymphocytes directed against basal keratinocytes or the basal membrane zone is assumed. Multiple therapeutic options exist: local and systemic corticosteroids, psoralens with ultraviolet A light (PUVA), retinoids, cyclosporin.

Diagnosis, Differential↗
PubMed2001

Teledermatology as a tool for communication between general practitioners and dermatologists.

A feasibility study of teledermatology was undertaken in Groningen. Six general practitioners (GPs) sent digital images by email, along with relevant patient information, to dermatologists at the Martini Ziekenhuis Groningen, a general non-academic hospital. The dermatologists returned their responses by email. A total of 89 cases were dealt with in this way. On average, the GPs took three photographs per patient. The time taken by the GP to produce and transmit the images, and to implement the telemedicine advice received from the dermatologist, was 9 min and 3 min, respectively. The time spent on diagnosis, provision of advice and response by email amounted to 10 min for the dermatologist. It was concluded that teleconsultations by email are feasible in the daily practice of GPs and dermatologists in a general non-academic hospital. Generally, GPs, dermatologists and patients were satisfied with teleconsultations. Furthermore, GPs reported that 63% of the teleconsultations were of educational value.

Attitude of Health Personnel↗
PubMed1998

[Benign symmetrical lipomatosis].

A man aged 51 for the last 3 months had displayed general malaise, epigastric pain, nausea, vomiting and constipation. Also, he had a pseudo-athletic appearance with symmetrical large accumulations of fat on the front of the trunk, the lower back, the shoulders and the proximal extremities, characteristic of 'benign symmetrical lipomatosis'. He died of embolism of the aortic bifurcation and autopsy revealed an extensive adenocarcinoma in the upper abdomen, probably originating from the pancreas or the stomach. Benign symmetrical lipomatosis mostly occurs in middle-aged men. The pathogenesis is unknown. Association with alcohol abuse, metabolic abnormalities, polyneuropathy and certain malignancies has been described. Treatment is symptomatic by surgery or liposuction.

Abdominal Neoplasms↗
PubMed1996

Cytogenetic findings in mouse multiple myeloma and Waldenström's macroglobulinemia.

Multiple myeloma (MM) and Waldenstrom's macroglobulinemia-like lymphoma (MW) appear spontaneously in C57BL/KaLwRij mice at a frequency of 0.5% and 0.2%, respectively. They can readily be propagated by intravenous transfer of mainly bone marrow or spleen cells into syngeneic recipients. Previous studies demonstrated that these mouse malignant monoclonal gammopathies (MMG) show clinical and biologic features that closely resemble those of the corresponding human diseases and thus could be used as experimental models. We report on cytogenetic analysis of two mouse MW and five MM in vivo cell lines of the 5TMM series propagated in syngeneic mice. These studies demonstrated clonal abnormalities in all cell lines, hyperdiploid karyotype in both MW and one MM lines, and hypotriploidy, hypertriploidy, or hypotetraploidy in the other lines. Structural abnormalities of chromosome 15 were observed in all MM lines. In five MM lines, frequent rearrangements were also found for chromosome numbers 1, 2, 5, and 12. A single chromosomal abnormality, as found in induced mouse plasmacytomas and resembling Burkitt lymphoma, was not found in mouse MM and MW. It was concluded that spontaneously originating C57BL MM of the 5T series is a better model for human MM than pristane-induced BALB/c or NZB plasmacytoma.

Animals↗
PubMed1992

Similarity between mycobacterial and human epidermal antigens.

Eight out of 17 mouse anti-Mycobacterium leprae monoclonal antibodies (MAb) were previously observed to react with human nerve and skin antigenic determinants in cryostat sections, using an indirect immunoperoxidase technique. These observations suggested that antigenic mimicry may be involved in the development of the clinical manifestations of leprosy. In the present study we have extended our earlier findings by investigating sera from leprosy patients and MAb using Western blot technique. It was observed that 30 sera and their corresponding F(ab')2 fragments from isolated IgG fractions of both tuberculoid and lepromatous patients reacted with 40-50 epidermal proteins of molecular weights (MW) ranging from 10 to 130 kDa. Sera from 14 controls, however, showed similar reactivity patterns. Absorption of nine patient and control sera with M. tuberculosis, M. marinum and M. kansasii resulted in the removal of several components of different MW in nine, four and three cases, respectively. No consistent differences between sera from leprosy patients and controls were observed. Four out of eight MAb against M. leprae which reacted with determinants in human epidermis and/or dermis in skin cryostat sections reacted with epidermal proteins of MW higher than 39 kDa in Western blot. Four MAb which showed reactivity in cryostat sections did not react in Western blot. Another four MAb did react with human epidermal proteins in Western blot but did not react in cryostat sections, indicating that the MAb were reacting with different epitopes in the two systems. Five MAb did not react with human epidermal proteins either in cryostat sections or in Western blot.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Isolation and molecular characterization of the B cells producing the paraprotein in a case of benign monoclonal gammapathy in C57BL mice.

Benign monoclonal gammapathy (BMG) is defined as a benign monoclonal B cell proliferative disorder characterized by the presence of a persisting component of homogenous immunoglobulins (H-Ig) in the serum. A possible role of antigenic stimulation in the development of BMG has been suggested. From a C57BL mouse, a murine model for BMG, we have isolated clonally related B cells in order to investigate the occurrence of somatic mutations in the variable heavy chain (VH) region of the genes of H-Ig-producing B cell clones. Therefore, B cells were immortalized by hybridoma technology. The hybridomas were screened for resemblance of the serum H-Ig component by Wieme agar electrophoresis, followed by immunoblotting and isoelectrofocusing. Clonal relationship was investigated by Southern blot analysis using a JH probe. In this way we isolated five hybridomas producing an IgG2a, kappa that was identical to the original serum H-Ig component according to testing with anti-idiotypic antisera. mRNA sequencing of four hybridomas showed only one base pair difference in the VH genes. This particular gene belonged to the J558 VH gene family. When compared to the most closely related known VH sequence, three base pair differences were found. The almost complete absence of base pair differences in the VH genes of the four sequenced hybridomas, compared with an independently derived hybridoma, suggests that the same germ-line VH gene has been used and that somatic mutations were infrequent in our BMG clone.

Animals↗
PubMed1990

The 5T mouse multiple myeloma model: absence of c-myc oncogene rearrangement in early transplant generations.

Consistent chromosomal translocations involving the c-myc cellular oncogene and one of the three immunoglobin loci are typical for human Burkitt's lymphoma, induced mouse plasmacytoma (MPC) and spontaneously arising rat immunocytoma (RIC). Another plasma cell malignancy, multiple myeloma (MM), arising spontaneously in the ageing C57BL/KaLwRij mice, was investigated in order to see whether the MM cells contain c-myc abnormalities of the MPC or RIC type. Rearrangement of the c-myc oncogene was found in the bone marrow cells only in 5T2 MM transplantation line in a mouse of the 24th generation and in none of the seven other MM of the 5T series which were of earlier generations. Since the mouse 5T MM resembles the human MM very closely, including the absence of consistent structural c-myc oncogene abnormalities, it can serve as a useful experimental model for studies on the aetiopathogenesis of this disease.

Animals↗
PubMed1990

Wood tars allergy, cross-sensitization and coal tar.

In a population of 1883 patients tested for allergic contact dermatitis (1985-1988), a prevalence of 5.4% (103 cases) was seen for wood tars (ICDRG allergen, 12% pet.) sensitization. In this group (n = 103), retrospectively, a combined allergy was seen to wood tars and fragrance mix in 43% and to wood tars and balsam of Peru in 31%. A combined allergy to wood tars and coal tar was seen in 19 patients (18.5%): 14 to liquor carbonis detergens (LCD), 8 to lianthral and 3 to both LCD and lianthral. Within the group with wood tars allergy (n = 103), a minority (n = 37) had a history of atopic dermatitis. Comparison of the test results in atopic and non-atopic subgroups (within the group of 103) revealed a higher incidence of combined wood tars-fragrance mix allergy in the atopic group (n = 37). In this group, a lower incidence of combined wood tars-coal tar sensitization was seen in comparison with the non-atopic group (n = 66). The authors believe that combined "wood tars-coal tar" allergy could be the consequence of cross-sensitization rather than due to long-term previous topical treatment with tar derivatives. The high % of cross-allergy between wood tars and fragrance mix emphasizes the role of wood tars as an important indicator allergen in perfume allergy.

Coal Tar↗
PubMed1990

Sensitization to fragrance materials in Indonesian cosmetics.

2 different groups of patients were patch tested with 2 test series (A and B) containing extracts of fragrance raw materials, traditionally used in Indonesian cosmetics. Series A consisted of diluted extracts of commercially available Indonesian fragrances. Series B consisted of extracts prepared in our department from corresponding indigenous flowers and fruits. Group 1 consisted of 32 patients positive to fragrance-mix, of whom 8 (25%) had positive tests to 1 or more of the different extracts of fragrance raw materials. Reactions were observed to extracts of: Rosa hybrida Hort (7); Canangium odoratum Baill (5); Citrus aurantifolia Swingle (4); Jasminum sambac Ait (2). 6 of the 8 patients had reactions to 1 or more of the components of fragrance-mix: oakmoss (3); cinnamic alcohol (2), isoeugenol (1); cinnamic aldehyde (1) and geraniol (1). Group 2 consisted of 159 patients patch tested on suspicion of contact dermatitis, who were fragrance-mix negative. Only 2 (1.2%) had a positive patch test to the extracts of fragrance raw materials. Specimens taken (as is) from the flowers and citrus fruits (being the basis sources of the fragrance raw materials) were less antigenic. The use of additional test series in Indonesia to detect allergy to traditional cosmetics and perfumes merits further investigation.

Allergens↗
PubMed1990

Contact allergy to spices.

A group of 103 patients suspected of contact allergy was tested with the European standard series, wood tars and spices: paprika, cinnamon, laurel, celery seed, nutmeg, curry, black pepper, cloves, white pepper, coriander, cacao and garlic. 32 patients (Group I) were selected on the basis of positive tests to one or more of possible indicators for allergy to spices: colophony, balsam of Peru, fragrance-mix and/or wood tars. 71 patients (Group II) showed no response to these indicators. In Group I (n = 32) a statistically significantly higher % of patients (47%) showed positive reactions to 1 or more spices, compared with 15% in Group II (N = 71). Among the spices, the highest numbers of reactions were found to nutmeg (28%), paprika (19%) and cloves (12%) in the indicator-positive Group I. Fragrance-mix turned out to be a particularly important indicator allergen, especially for paprika, nutmeg and cloves. The contact allergy in 11 out of 32 (Group I) and 7 out of 25 patch-tested patients (recruited from Group II) appeared to be directed mainly against the ether-extractable volatile fractions of the spices.

Condiments↗
PubMed1989

Modulation of total IgE levels in serum of normal and athymic nude BALB/c mice by T cells and exogenous antigenic stimulation.

Several different grades of T-system impairment were studied for their effects on the total serum IgE concentration in BALB/c mice. Homozygous athymic nu/nu mice and their heterozygous nu/+ littermates were compared for serum IgE levels while kept under either barrier-maintained or conventional conditions. The results show a paradox between the T-cell dependency of the IgE immune response and the increased levels of serum IgE in the absence of T cells. Both barrier-maintained and conventionalized nu/nu mice have at least twofold increased serum IgE levels as compared to nu/+ mice. With age, IgE levels increased faster and reached higher plateau values in nu/nu than nu/+ mice. Moreover, after adult thymectomy of BALB/c mice the serum IgE levels increased up to 15-fold at 4 months of age, while infusion of immunocompetent T cells in nude mice resulted in a 2- to 5-fold decrease of the IgE level.

Aging↗
PubMed1989

Detection of oncogene expression by fluorescent in situ hybridization in combination with immunofluorescent staining of cell surface markers.

To study oncogene expression in heterogeneous cell populations we developed and optimized a non-radioactive in situ hybridization technique using biotinylated single-stranded RNA probes and combined this technique with immunofluorescent staining of cell surface markers. As a model for our studies we used HL60 cells. In these cells we detected c-myc mRNA molecules by in situ hybridization following staining of the pan myeloid cell surface marker CD33, by a monoclonal antibody. Hybrids were detected by streptavidin-FITC and CD33 by a TRITC-conjugated antibody. Controls involved pretreatment with RNAase, hybridization with sense RNA probes and blocking with an excess of unlabeled antisense probes. The integrity of the RNA in the cell was shown by hybridization with the GAPDH antisense probe. Essential for successful double-labeling was the choice of a fixation procedure that was suitable for the in situ hybridization and mild enough not to destroy the cell surface marker staining. This fluorescent in situ hybridization in combination with cell surface marker staining will be useful for studying gene expression in phenotypically well-defined cell populations.

Antigens, CD↗
PubMed1988

The influence of T cells on homogeneous immunoglobulins in sera of athymic nude mice during aging.

In this study, results are presented which are in agreement with predictions made on basis of the 'three-stage hypothesis' on the development of benign monoclonal gammapathy (BMG). In a T-cell depletion model. C57BL/Ka nude mice were shown to develop single and multiple homogeneous immunoglobulins (H-Ig) during aging in the highest frequencies known so far. Ninety per cent of the C57BL/Ka nude mice displayed one or more H-Ig at 12 months of age. In a T-cell supplementation model, infusion of corticosteriod resistant T cells into 9-month-old BALB/c nude mice resulted in a decrease in the frequency of H-Ig from 43% at 9 months down to 20% at 15 months of age. In contrast, the frequency of H-Ig in the control group increased from 40% at 9 months up to 68% at 12 months. The results show that normally functioning T cells are essential for the generation of a normal, heterogeneous Ig spectrum; they further support the validity of the three-stage hypothesis with regard to the role of an impairment of the T immune system in the pathogenesis of BMG.

Aging↗
PubMed1988

Influence of long-term antigenic stimulation started in young C57BL mice on the development of age-related monoclonal gammapathies.

Long-term antigenic stimulation by multiple antigens (DNP conjugated to human serum albumin (DNP-HSA), ovalbumin and pneumococcal polysaccharide) without adjuvant in young C57BL mice resulted in the development of homogeneous immunoglobulins (H-Ig) during aging in frequencies higher than those in the control group. Our data showed that antigen-specific B-cell clones were at least in part responsible for this increased incidence of age-related monoclonal gammapathies (MG). Using in situ adsorption performed on Wieme's agar plates and in immunoelectrophoresis, antibody activity to one of the immunizing agents (DNP-HSA) could be demonstrated within 10% of the in old mice appearing H-Ig components. This frequency was significantly different from the 0.3% of the H-Ig components of the aging control mice. The antigen-specific MG belonged most likely to the category of benign MG. These findings indicate that long-lasting antigenic stimulation contributes to the development of age-related B-cell proliferative disorders, namely of the benign MG.

Aging↗
PubMed1988

The influence of genetic factors associated with the immunoglobulin heavy chain locus on the development of benign monoclonal gammapathy in ageing IgH-congenic mice.

The role of genetic factors associated with the immunoglobulin heavy chain locus (Igh) in the development of benign monoclonal gammapathy (BMG), a benign B-cell proliferative disorder, was investigated in six Igh congenic mouse strains during ageing. The strains used had a C57BL or BALB background: C57BL/6, BALB.Igb and CB-20 carrying the C57BL Igh (Ighb allotype), BALB/c and C57BL/6.Iga carrying the BALB/c Igh (Igha allotype) and BAB-14, that is of BALB/c origin with the exception of the constant part of the Igh, which is of C57BL origin. The frequency of homogeneous immunoglobulins (H-Ig), both single and multiple, was the highest in C57BL/6 mice, followed by C57BL/6.Iga. The frequencies of H-Ig in BALB.Igb and CB-20 mice were higher than those of BALB/c and BAB-14, although somewhat lower than in C57BL/6.Iga mice. Multiple H-Ig were found especially in the sera of C57BL/6 mice. Categorization of the monoclonal gammapathies (MG) on the basis of their origin showed a single transient monoclonal B-cell proliferation in 0-8% of the mice of all strains. Persistent, non-progressive MG, presumably BMG, were detected in 64% of C57BL/6, 30% of C57BL/6.Iga, 22% of BALB.Igb, 17% of CB-20, 13% of BAB-14 and 6% of BALB/c mice. Multiple myeloma or Waldenström-like B-cell lymphoma were found to be responsible for 2-4% of the paraproteinemias in all strains. The remaining H-Ig, varying from 11% of the C57BL/6 to 70% of the BAB-14 mice, could not be evaluated in time. The most frequent isotypes of the BMG within C57BL/6 and C57BL/6.Iga were IgG2a and IgG2b, respectively; IgM was the most frequent isotype within the four BALB congenic strains. The immunoglobulin heavy chain allotypes under investigation appeared to be only partly related to the onset, occurrence, multiplicity and persistence of the BMG developing in these Igh congenic C57BL and BALB strains during ageing. The immunoglobulin heavy chain allotypes, however, were not related to the major isotype of the BMG. The results obtained in CB-20 and BALB.Igb on the one hand, and in BAB-14 on the other hand, may suggest a role for the variable part of the Igh in the development of BMG. Since no absolute influence could be ascribed to the Igh, we assume that primarily other genetic sequences regulating proliferative B-cell functions account for the pathogenesis of BMG.

Aging↗
PubMed1987

The influence of H-2 genetic factors on the development of benign monoclonal gammopathy in ageing H-2 congenic C57BL and BALB mice.

The role of H-2 genetic factors in the development of benign monoclonal gammopathy (BMG) was investigated in six H-2 congenic C57BL and BALB strains (C57BL/10.ScSn and BALB.B: H-2b; B10.D2 and BALB/c: H-2d; B10.BR and BALB.K: H-2k) during ageing. The frequencies of homogeneous immunoglobulins (H-Ig), both single and multiple, in the three C57BL strains were higher than those in the corresponding three BALB strains. No relationship was found with a particular H-2 haplotype. The most frequent H-Ig isotype within the C57BL strains was IgG2a, within BALB.B and BALB.K mice IgG3 and in BALB/c mice IgG1. Categorization of the monoclonal gammopathies (MG) on the basis of their origin showed a single transient monoclonal B-cell proliferation in 2-5% and 3-9% of the C57BL and BALB mice positive for H-Ig, respectively. Multiple myeloma or B-cell lymphoma were found to be responsible for about 1% of the paraproteinaemias in all strains. Persistent, non-progressive MG, most likely BMG, was detected in 70-81% and 39-46% of the C57BL and BALB mice positive for H-Ig, respectively. The remaining 14-24% and 50-58% of the, respectively, C57BL and BALB mice positive for H-Ig could not be evaluated in time. The H-2 haplotypes under investigation were not associated with the onset, occurrence, multiplicity, persistence or isotype of the MG developing in these H-2 congenic C57BL and BALB strains during ageing.

Aging↗